Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL⁻¹ silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.

Hippo signaling is a highly conserved pathway central to diverse cellular processes. Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers. Recent studies have uncovered that, in addition to the classical signaling cascade regulation, biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling. In this review, we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation, with a particular focus on transcriptional activation mediated by Yes-associated protein (YAP)/transcriptional coactivator with post-synaptic density-95, disks-large, and zonula occludens-1 (PDZ)-binding domain (TAZ) condensates. Furthermore, we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma (FUS) in modulating the biophysical properties of TAZ condensates, which in turn influence their transcriptional activity and pro-tumorigenic functions. These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity.
Humans ; Signal Transduction ; Hippo Signaling Pathway ; Protein Serine-Threonine Kinases/physiology* ; Animals ; Biomolecular Condensates/metabolism* ; Transcription Factors/metabolism* ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing/metabolism* ; Neoplasms ; Transcriptional Activation ; Intracellular Signaling Peptides and Proteins/metabolism*

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

Yttrium-90(90Y)selective internal radiation therapy(SIRT)is an emerging modality for the treatment of hepatocellular carcinoma(HCC),leveraging the nuclide 90Y to deliver targeted radiation therapy.90Y has a long half-life and can be used to selectively ablate tumor cells by high-energy beta rays.It has high biological effectiveness and robust local control capabilities.In recent years,with the continuous advancement of basic and clinical research,the application of 90Y-SIRT in the conversion treatment of unresectable HCC(uHCC)has made significant progress.However,challenges remain in the clinical application of 90Y-SIRT,including how to improve the efficacy of conversion therapy and how to optimize therapy regimens.This review aims to summarize the research progress of90Y-SIRT in the conversion therapy of uHCC.

Objective To explore the effects of mental fatigue on attention maintenance function by electroencephalogram(EEG)signal characteristics and cortical source analysis.Methods A total of 25 healthy males were recruited as subjects and contingent negative variation(CNV)auditory paradigm was used to assess the differences in EEG characteristics before and after mental fatigue,with the average amplitude of CNV at different processing stages as the analysis indices.Then,the 3-dimensional distribution of cortical current density changes of CNV after mental fatigue were calculated by standardized low-resolution electromagnetic tomography analysis(sLORETA).Results The reaction time of the CNV signal remained unchanged following mental fatigue(P＞0.05),while the lapse rate exhibited a significant increase(P＜0.05).Besides,mental fatigue was related to a notable decrease in the amplitude of CNV early components(500-1 000 ms after warning stimulus)at the central and central parietal electrodes,and a significant reduction in the amplitude of CNV late components(2 550-3 050 ms after warning stimulus)at the prefrontal,frontal,central,and central parietal electrodes(all P＜0.05).The results of sLORETA source analysis showed that the brain activity in the left posterior insular cortex decreased after mental fatigue during the late component of CNV(P＜0.05).Conclusion The decreased activation of the posterior insula,which plays a crucial role in sensorimotor information integration,could potentially serve as a neural mechanism for the reduction of CNV amplitude and the impairment of attention maintenance function following mental fatigue.

Objective:To analyzed the chemical components of Black Tartary Buckwheat using Ultra-performance liquid chromatography coupled with quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive Orbitrap MS); To further compared the compositional differences under various drying conditions.Methods:UPLC-Q-Exactive Orbitrap MS was employed to scan 14 samples of Black Tartary Buckwheat in 4 batches, aiming to identify the major chemical components. ACQUITY UPLC HSS T3 C18 column (2.1 mm×100 mm, 1.7 μm) was adopted; mobile phase was 0.1% formic acid aqueous solution-acetonitrile solution; flow rate was 0.3 ml/min for gradient elution; HESI-Ⅱ ion source was used to detect negative ions. According to general mass spectroscopy rules and literature, at the same time, Compound Discoverer 3.2 and MSConvert software were used to analyze the data, upload to GNPS network, and finally generate network diagram using Cytocape 3.6.1 software.Results:A total of 134 components were identified in Black Tartary Buckwheat, of which 76 compounds were identified in the negative ion mode, 79 compounds were identified in the positive ion mode, and 21 chemicals were simultaneously identified as positive and negative ions. Based on the similarity cluster analysis of UPLC-Q-Exactive Orbitrap MS secondary mass spectrometry fragment patterns, a molecular network was established, and the main compounds in Black Tartary Buckwheat were flavonoids, phenolic acids and amino acids, and the results showed that the positive and negative ion modes had similar clustering results. There were certain differences in the content of flavonoids, phenolic acids, and amino acids in Black Tartary Buckwheat under two different drying conditions.Conclusion:The established UPLC-Q-Exactive Orbitrap MS method enables rapid identification of the main chemical components in Black Tartary Buckwheat, while the constructed molecular network provides a reference framework for further research on its chemical composition. Additionally, the drying conditions are found to exert certain effects on the content of these chemical components.

The morphological characteristics of hepatocellular carcinoma(HCC)tumor margins are pivotal in influencing patient's prognosis and the selection of therapeutic strategies.This paper re-viewed the classification methods of HCC tumor margins,ranging from traditional macroscopic classifi-cations to refined classification systems based on multi-omics analysis,and analyzed the role of these classification methods in guiding the formulation of personalized treatment plans.Additionally,this paper emphasized the crucial role of three-dimensional imaging techniques in assessing tumor margin morphology and outlined future research directions,including validating the effectiveness of multi-omics classification systems and developing new imaging and molecular biomarkers to achieve more precise treatment plans and prolong patient survival.

Objective:To explore the factors influencing the supportive communication ability of medical undergraduates, and to propose strategies to improve supportive communication.Methods:By cluster sampling, we selected 388 medical undergraduates of grades 2017 and 2018 from Harbin Medical University for a questionnaire survey on supportive communication, general self-efficacy, and health education abilities. SPSS 22.0 was used for descriptive statistical analysis. AMOS 22.0 was used to construct a structural equation model to verify the relationship between the three variables. Mediating effects were also tested.Results:The students showed good supportive communication ability, with a total score of (74.28±10.84) points. The general self-efficacy score was (27.81±5.58) points, and the total score of health education ability was (25.50±4.76) points. General self-efficacy had direct positive effects on supportive communication and health education abilities ( β=0.75, 0.31, both P<0.001). Health education ability had a direct positive effect on supportive communication ability ( β=0.14, P<0.001). Health education ability played a significant mediating role in the influence of general self-efficacy on supportive communication ability (standardized mediating effect value=0.042, P<0.01), with the mediating effect accounting for 5.1%. Conclusions:The health education competency of medical undergraduates can mediate the effect of general self-efficacy on supportive communication ability. By strengthening medical humanities education to increase general self-efficacy and also emphasizing the cultivation of health education competency, the supportive communication ability of students can be improved.

Stomach exuberance and spleen deficiency are common pathogenesis of many metabolic diseases. Through analyzing the pathogenesis of stomach exuberance and spleen deficiency， it is believed that its essence is stomach heat and spleen deficiency. Stomach heat includes gastrointestinal heat， spleen and stomach damp-heat， and spleen deficiency is divided into deficiency of spleen yin， deficiency of spleen qi ， and deficiency of spleen yang. It is suggested that the metabolic diseases of stomach-exuberance and spleen-deficiency syndrome can be divided into three categories，i.e. stomach-heat and spleen yin-deficiency， stomach-heat and spleen qi-deficiency， and stomach-heat and spleen yang-deficiency， and the main treatment methods are clearing and draining heat， nourishing yin and moistening intestine， clearing dampness and heat， strengthening spleen and qi， clearing dampness and heat， strengthening spleen and warming yang， respectively， with prescriptions as Maziren Pills （麻子仁丸）， Qinlian Pingwei Powder （芩连平胃散）， and Jiawei Lianli Decoction （加味连理汤） accordingly.

Objective Chlorination is often used to disinfect recreational water in large amusement parks;however,the health hazards of chlorination disinfection by-products(DBPs)to occupational populations are unknown.This study aimed to assess the exposure status of chlorinated DBPs in recreational water and the health risks to employees of large amusement parks. Methods Exposure parameters of employees of three large amusement parks in Shanghai were investigated using a questionnaire.Seven typical chlorinated DBPs in recreational water and spray samples were quantified by gas chromatography,and the health risks to amusement park employees exposed to chlorinated DBPs were evaluated according to the WHO's risk assessment framework. Results Trichloroacetic acid,dibromochloromethane,bromodichloromethane,and dichloroacetic acid were detected predominantly in recreational water.The carcinogenic and non-carcinogenic risks of the five DBPs did not exceed the risk thresholds.In addition,the carcinogenic and non-carcinogenic risks of mixed exposure to DBPs were within the acceptable risk limits. Conclusion Typical DBPs were widely detected in recreational water collected from three large amusement parks in Shanghai;however,the health risks of DBPs and their mixtures were within acceptable limits.